Vacuole-inducing compounds that disrupt endolysosomal trafficking stimulate production of exosomes by glioblastoma cells.
Vacuole-inducing compounds that disrupt endolysosomal trafficking stimulate production of exosomes by glioblastoma cells.
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DOI：
10.1007/s11010-017-3130-x
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发表时间：
2018-03
影响因子：
4.3
通讯作者：
Maltese WA
中科院分区：
文献类型：
--
作者：
Li Z;Mbah NE;Maltese WA
外泌体是由哺乳动物细胞产生的，当多泡内体与质膜融合，释放出它们的腔内囊泡。在这项研究中，我们评估了MOPIPP（一种新型吲哚基查尔酮）和液泡素-1（一种独特的三嗪基化合物）对培养胶质母细胞瘤和293T细胞外泌体产生的影响。这两种化合物都能促进核内体晚期腔室的空泡化，并干扰核内体晚期向溶酶体的运输，但没有明显的细胞毒性。结果表明，用这些化合物处理的液泡细胞释放的外泌体的形态与未处理的对照组相似。然而，这两种化合物在从相同数量的细胞中收集的外泌体部分中触发外泌体标记蛋白（例如CD63， Alix）释放的数倍增加。尽管外泌体的产量显著增加，但在用化合物处理的细胞中，外泌体携带的选定miRNA货物的谱通常相似。就MOPIPP和液泡素-1似乎能够增加培养细胞外泌体的总体产量而言，它们可能有助于开发基于外泌体的治疗方法。
Exosomes are produced from mammalian cells when multivesicular endosomes fuse with the plasma membrane, releasing their intralumenal vesicles. In this study we assessed the effects of MOPIPP, a novel indole-based chalcone, and vacuolin-1, a distinct triazine-based compound, on exosome production in cultured glioblastoma and 293T cells. Both compounds promote vacuolization of late endosome compartments and interfere with trafficking of late endosomes to lysosomes, without significant cytotoxicity. The results show that vacuolated cells treated with these compounds release exosomes with morphologies similar to untreated controls. However, both compounds trigger multi-fold increases in release of exosome marker proteins (e.g., CD63, Alix) in exosome fractions collected from equivalent numbers of cells. Despite the marked increase in exosome production, the profiles of selected miRNA cargoes carried by the exosomes were generally similar in cells treated with the compounds. Insofar as MOPIPP and vacuolin-1 seem able to increase the overall yield of exosomes from cultured cells, they might be useful for efforts to develop exosome-based therapeutics.
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影响因子：
13.3
作者：
Lu Y;Dong S;Hao B;Li C;Zhu K;Guo W;Wang Q;Cheung KH;Wong CW;Wu WT;Markus H;Yue J
通讯作者：
Yue J
DOI：
10.1016/j.apsb.2016.02.001
发表时间：
2016-07
期刊：
Acta pharmaceutica Sinica. B
影响因子：
--
作者：
Ha D;Yang N;Nadithe V
通讯作者：
Nadithe V
影响因子：
4.8
作者：
Savina, A;Furl치n, M;Colombo, MI
通讯作者：
Colombo, MI
影响因子：
4
作者：
Johnson, EE;Overmeyer, JH;Maltese, WA
通讯作者：
Maltese, WA
DOI：
10.1083/jcb.201212113
发表时间：
2013-02-18
期刊：
The Journal of cell biology
影响因子：
--
作者：
Harding CV;Heuser JE;Stahl PD
通讯作者：
Stahl PD